HIF-1α,COX-2 Expression In Breast Cancer And Its Relationship With Lymph Node Metastasis

Objective: Breast cancer is one of the most common malignancy of women in recent years, the incidence of breast cancer increased year by year, seriously endangering the general health of women. Early surgical treatment of breast cancer, postoperative radiotherapy, chemotherapy and endocrine therapy is commonly used in clinical treatment, the prognosis of patients plays an important role .distant metastasis is the main reason affecting the prognosis of breast cancer. The lymph node metastasis is an important form of early breast cancer metastasis. Found to predict a new indicator for prognosis of breast cancer and to clarify the mechanism of lymph node metastasis of breast cancer in the prevention and treatment of lymph node metastasis in breast cancer has important clinical significance. HIF-1αby regulating genes associated with hypoxia-induced expression can promote tumor energy metabolism, vascular generation and so on tumor growth and metastasis plays an important role. COX-2 can enhance the invasive ability of tumor cells, studies have shown, COX-2 high expression of MMP -2 activity can increase, increased expression of membrane metalloproteinases are conducive to tumor invasion and lymph node metastasis. This study was designed by immunohistochemical methods to analyze HIF-1α, COX-2 expression in breast cancer tissues, and explore its expression levels and cancer clinical staging and pathological grading of the relationship between, and between its occurrence in tumor development and progression in synergy to provide a new treatment for clinical basis.Methods: the Second Hospital of Hebei Medical University, Department of Pathology, from February 2006 to February 2009 of 92 cases of surgical removal of paraffin-embedded specimens of breast cancer. And to collect the same period 16 cases of non-cancerous breast tissue as a control group. The age of 32 years old -78 years old, with a median age of 53 years. Tumor diameter, 2-8cm; axillary lymph node 47 positive cases , 45 negative cases ; breast cancer, pathological type, histological grade of breast tumors according to WHO histological classification (2003 version) standards. Basis of International Union Against Cancer (UICC) of breast cancer TNM staging criteria (2003) were divided into group stageⅠ(T1N0M0) (12cases),Ⅱstage group (T0~ 1N1M0, T2N0 ~ 1M0, T3N0M0) (57 cases),Ⅲstage group (T0 ~ 2N2M0, T3N1 ~ 2M0 T4 any NM0, any T N3M0) (23 cases). Conventional paraffin-embedded tissue block, 4um serial sections for 5, in which a slice of conventional HE staining pathological morphology, the remaining four for the HIF-1αand COX-2 specific antibody immune staining, as well as negative control. The immunohistochemical method to detect HIF-1α, COX-2 in breast cancer tissue expression. Comprehensive data analysis of clinical data, applications SPSS13.0 software dataχ~2 test, the trend chi-square test and Spearman rank correlation testing method of the research results were analyzed statistically. Test for P <0.05 statistically significant.Results:1 HIF-1αexpression: 16 cases of non-cancerous breast tissue expression of HIF-1αwere negative. 92 cases of breast cancer, there are 49 cases of positive expression, breast cancer group of HIF - 1αpositive rate is higher than non-cancerous breast tissue group, there was significant difference (χ~2 = 15.5996, P <0.0001) of breast cancer Histological grading:Ⅰlevel positive expression rate of 36.36% ( 12/ 33)Ⅱ-level positive expression rate of 58.54% ( 24/ 41)Ⅲgrade positive expression rate of 13% (13/ 18) by theχ~2 test differences among the three groups was statistically significant (χ~2 = 6.8430, P =0.0327) Further line spearman rank correlation analysis confirmed that HIF-1αexpression and histological grade of breast cancer was positively correlated(r=0.345 P=0.001 ) of breast cancer TNM staging:Ⅰperiod of positive expression rate of 41.67% (5/ 12)Ⅱperiod of positive expression rate of 52.63% (30/57)Ⅲperiod of positive expression rate of 60.87% (14/23) by theχ~2 test differences among the three groups are not significance statistically (χ~2 = 1.1919, P=0.551) lymph node-positive rate of HIF-1αexpression as 72.34%, lymph node-negative group the rate of HIF-1αexpression as33.33% byχ~2 test statistical difference between the two groups significance (χ~2 =14.0514, P =0.0002)2. COX-2 expression: 16 cases of non-cancerous breast tissue expression of COX-2 were two positive. There are 48cases of breast cancer patients with positive expression of COX-2 . Breast cancer group was higher than non-cancerous breast tissue group, there was significant difference (χ~2 = 8.6287, P =0.0033). Histological grade in breast cancer:Ⅰlevel positive expression rate of% 39.39(13/33)Ⅱ-level positive expression rate of53.66% (22/41)Ⅲgrade positive expression rate of 72.22% (13/18) by theχ~2 test differences among the three groups was statistically significant (χ~2 = 10.8963, P =0.0043), Further line spearman rank correlation analysis confirmed that COX-2 expression and histological grade of breast cancer was positively correlated(r=0.250,P=0.016 ) TNM staging of breast cancer:Ⅰperiod of positive expression rate of33.33% (4/12)Ⅱperiod of positive expression rate of43.86% (25/57)Ⅲperiod of positive expression rate of82.61% (19/23 ) by theχ~2 test differences between the three groups was statistically significant (χ~2 = 11.824, P=0.0027) Further line spearman rank correlation analysis confirmed that COX-2 expression and TNM staging of breast cancer was positively correlated(r=0.395 P<0.01 ) lymph node metastasis in breast cancer: lymph node metastasis group of COX-2 positive expression rate of70.21%, lymph node-negative group of COX-2 The positive expression rate of33.33%, byχ~2 test differences between the two groups was statistically significant (χ~2 = 12.5306, P =0.0004)3. Correlation analysis showed that in breast cancer HIF-la protein and COX-2 protein expression was positively correlated, the correlation coefficient r = 0.324, P=0.002,Conclusion:1 Compared with the non-cancerous breast tissue, HIF-1α, COX-2 expression in breast cancer tissues increased, to a certain extent, reflecting the differentiation and metastasis of tumor tissue, having some significance to the clinical prognosis.2 HIF-1α, COX-2 expression is closely related to pathological grade, and with the HIF-1α, COX-2 expression increased, gradually increase the degree of malignancy of breast cancer.3 HIF-1α, COX-2 in lymph node metastasis-positive group was significantly higher than those without lymph node metastasis group4 HIF-1α, COX-2 expression in breast cancer correlation exists, suggesting that both the development process in the tumor there is a certain synergy.